BINDING ENERGY TRANSDUCTION IN ENZYMATIC CATALYSIS

酶催化中的结合能转换

• 批准号: 2184508
• 负责人: Harvey F. Fisher
• 金额: $ 9.71万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2184508
• 关键词: NAD(H) phosphate; alcohol dehydrogenase; biological signal transduction; calorimetry; chemical binding; enzyme complex; enzyme mechanism; enzyme model; glutamate dehydrogenase; nicotinamide adenine dinucleotide; protein denaturation; protein structure function; temperature; thermodynamics

The idea that enzyme-ligand-binding energy can be utilized to drive catalytic steps is a widely held concept, but one that has not been susceptible to direct experimental testing. We have discovered a highly ethalpic two-state macroscopic transition in glutamate dehydrogenase and its complexes which appears to be responsible for the appearance of large deltaCp's. We have developed a unified model which explains a variety of thermodynamic phenomena of pyridine- nucleotide dehydrogenases. On this basis, we now have extended that model to account for free energy transduction in enzymatic catalysis. In more recent work we have found that rather than a single ligand binding induced transition, each enzyme form contains two such transitions, each affected by a given set of ligands. The two transitions are coupled to each other in a complex fashion and their energetics are tightly coupled to that of the thermal unfolding of the protein. Using newly available technology, we hope to obtain definitive evidence for the existence, nature, and scope of occurrence of such transitions, discover the precise manner of their coupling, and explore their possible function as components of the energy transduction machinery of enzymes.

酶-配体结合能可以用来驱动

项目成果

The existence of a hexameric intermediate with molten-globule-like properties in the thermal denaturation of bovine-liver glutamate dehydrogenase.

牛肝谷氨酸脱氢酶热变性过程中存在具有熔球状特性的六聚体中间体。

• DOI: 10.1016/s0301-4622(96)02192-8
• 发表时间: 1996
• 期刊: Biophysical chemistry
• 影响因子: 3.8
• 作者: Singh,N;Liu,Z;Fisher,HF
• 通讯作者: Fisher,HF

The real-time resolution of proton-related transient-state steps in an enzymatic reaction. The early steps in the oxidative deamination reaction of bovine liver glutamate dehydrogenase.

• DOI: 10.1016/s0021-9258(18)54109-0
• 发表时间: 1993-01
• 期刊: The Journal of biological chemistry
• 作者: N. Singh;S. Maniscalco;H. F. Fisher